A Line of Mice Selected for High Blood Ethanol Concentrations Shows Drinking in the Dark to Intoxication

Abstract

Background Many animal models of alcoholism have targeted aspects of excessive alcohol intake (abuse) and dependence. In the rodent, models aimed at increasing alcohol self-administration have used genetic or environmental manipulations, or their combination. Strictly genetic manipulations (e.g., comparison of inbred strains or targeted mutants, selective breeding) have not yielded rat or mouse genotypes that will regularly and voluntarily drink alcohol to the point of intoxication. Although some behavioral manipulations (e.g., scheduling or limiting access to alcohol, adding a sweetener) will induce mice or rats to drink enough alcohol to become intoxicated, these typically require significant food or water restriction or a long time to develop. We report progress toward the development of a new genetic animal model for high levels of alcohol drinking. Methods High Drinking in the Dark (HDID-1) mice have been selectively bred for high blood ethanol concentrations (BEC, ideally exceeding 100 mg%) resulting from the ingestion of a 20% alcohol solution. Results After 11 generations of selection, more than 56% of the population now exceeds this BEC after a 4-hour drinking session in which a single bottle containing 20% ethanol is available. The dose of ethanol consumed also produced quantifiable signs of intoxication. Conclusions These mice will be useful for mechanistic studies of the biological and genetic contributions to excessive drinking.

Ethanol Withdrawal-Associated Drinking and Drinking in the Dark: Common and Discrete Genetic Contributions

“…The genetically heterogeneous stock HS/Npt was the foundation and is the control population for HDID-1; HS mice were from the 71st filial generation (G71). Derivation of the HS and selection of HDID-1 have been described elsewhere [8]. All mice were naive at the time of testing.…”

“…These have been described extensively elsewhere [6-8]. Mice were given access to a single tube of 20% ethanol v/v in lieu of their water for 2 hr starting 3 hr into their circadian dark phase.…”

“…A subsequent survey of 12 inbred strains showed substantial genetic variability in DID as assessed by both intake and BEC [7]. Further establishing a genetic basis for DID, we successfully bred a line of High Drinking in the Dark (HDID-1) mice by mating those animals that reached the highest BECs after DID [8]. Heritability of the DID trait is substantially less than that of two-bottle preference drinking; however, HDID mice drink to higher BECs than C57BL/6J mice [8].…”

“…Further establishing a genetic basis for DID, we successfully bred a line of High Drinking in the Dark (HDID-1) mice by mating those animals that reached the highest BECs after DID [8]. Heritability of the DID trait is substantially less than that of two-bottle preference drinking; however, HDID mice drink to higher BECs than C57BL/6J mice [8]. Both genotypes display behavioral signs of intoxication after DID [6-8].…”

“…Heritability of the DID trait is substantially less than that of two-bottle preference drinking; however, HDID mice drink to higher BECs than C57BL/6J mice [8]. Both genotypes display behavioral signs of intoxication after DID [6-8]. …”